Merkel Cell Carcinoma in Solid Organ Transplant Recipients: Prognosis and Response to Immunotherapy

Merkelcell.org Summary

People with weakened immune systems, such as patients who have solid organ transplants, are at higher risk of getting Merkel cell carcinoma (MCC). As the number of transplants around the world grows, doctors expect more cases of MCC in this group. Immunotherapy, a drug that helps fight cancer by boosting the immune system, has been effective in about half of MCC patients with healthy immune systems. But it is less clear how safe or effective it is for transplant patients, since they are usually not included in clinical trials.

This study looked at 1,214 MCC patients, including 37 transplant patients and 1,177 non-transplant patients. Compared to others, transplant patients were more likely to be diagnosed with MCC that had already spread (76% vs. 51%) and generally had worse outcomes. Within two years, 70% of transplant patients developed cancer that spread far from the original site, compared to 25% of other patients. On average, transplant patients lived about 2.7 years after being diagnosed with MCC.

Eight kidney transplant patients received immunotherapy. Five (63%) saw their cancer shrink or disappear. However, two (29%) lost their transplanted kidney and needed dialysis to survive.

Overall, transplant patients with MCC often face more aggressive disease and harder treatment decisions. For kidney transplant patients, immunotherapy may still be an option, though it carries risks. For those with liver or heart transplants, the risks are greater, since those organs cannot be replaced with alternatives like dialysis. These findings highlight the importance of careful, shared decision-making between patients and their care teams.

Abstract

Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer with an increased risk of occurrence in immunocompromised patients, including solid organ transplant recipients (SOTR). As the number of SOTR rises worldwide, MCC cases in this population are also expected to increase. While anti-programmed death-(ligand)1 (anti-PD-(L)1) immunotherapy generates durable tumor responses in ∼50% of immunocompetent (IC) patients with advanced MCC, its efficacy and safety in SOTR remain uncertain as these patients have been excluded from most clinical trials.

Objectives: To compare baseline characteristics and outcomes among SOTR and IC patients with MCC, and to evaluate efficacy and toxicity of anti-PD-(L)1 in SOTR.

Methods: We queried a MCC registry from our institution (April 1988-May 2024), extracting data on demographics, anti-PD-(L)1 response, immunosuppression regimens, and incidence of allograft rejection and failure for analysis.

Results: We identified 1214 MCC patients (37 SOTR and 1177 IC patients); 8 of 37 SOTR received anti-PD-(L)1. The median time from solid organ transplant to MCC diagnosis was 10 years (range 0.4-43). The proportion of patients with advanced MCC (≥ stage III) was 76% in SOTR compared to 51% in IC patients (p=0.004). SOTR status was associated with worse outcomes, including higher rates of disease progression (adjusted hazard ratio [aHR] 2.3), MCC-specific mortality (aHR 3.0), and overall mortality (aHR 3.9; all p<0.001). The median time to death due to MCC for SOTR was 2.7 years; 24% of SOTR died within one year of diagnosis, in contrast to just 4% of IC patients. The median time to MCC progression for SOTR was 8.6 months vs 12 years for IC patients. Among SOTR, 70% developed distant metastases within 2 years versus 25% of IC patients. All eight MCC SOTR treated with anti-PD-(L)1 were kidney transplant recipients, with 5 (63%) experiencing an objective response (CR: 2, PR: 3). However, 2 (29%) patients experienced irreversible graft failure within 9 weeks.

Conclusions: SOTR status is a significant independent risk factor of a worse prognosis for MCC. This study represents the largest cohort evaluating the efficacy and safety of anti-PD-(L)1 in SOTR with advanced MCC, highlighting the potential benefits in this population.